Merkel Cell Polyoma Virus and Cutaneous Human Papillomavirus Types in Skin Cancers: Optimal Detection Assays, Pathogenic Mechanisms, and Therapeutic Vaccination

Abstract

Oncogenic viruses are recognized to be involved in some cancers, based on very well-established criteria of carcinogenicity. For cervical cancer and liver cancer, the responsible viruses are well-known (e.g., HPV, HBV); in the case of skin cancer, there are still many studies which are trying to identify the possible viral etiologic agents as principal co-factors in the oncogenic process. We analysed scientific literature published in the last 5 years regarding mechanisms of carcinogenicity, methods of detection, available targeted therapy, and vaccination for Merkel cell polyomavirus, and beta human papillomavirus types, in relation to skin cancer. This review is targeted at presenting the recent findings which support the involvement of these viruses in the development of some types of skin cancers. In order to optimize the management of skin cancer, a health condition of very high importance, it would be ideal that the screening of skin cancer for these two analysed viruses (MCPyV and beta HPV types) to be implemented in each region’s/country’s cancer centres’ molecular detection diagnostic platforms, with multiplex viral capability, optimal sensitivity, and specificity; clinically validated, and if possible, at acceptable costs. For confirmatory diagnosis of skin cancer, another method should be used, with a different principle, such as immunohistochemistry, with specific antibodies for each virus.

The Influence of Oncogenic Viruses in Renal Carcinogenesis: Pros and Cons

“…Polyomaviridae is a family of small, icosahedral, non-enveloped viruses, with a double-stranded DNA genome, 5 kbp in length, the DNA packed together with histones belonging to the host cells. These viruses infect species of mammals, birds and fish [ 9 ]. It is considered one family which probably has oncogenic members that could be causative in the development of urothelial tumors.…”

“…Polyomaviruses are also analyzed in association with some cancers: MCPyV was first discovered clonally integrated in Merkel cell carcinoma [ 9 ], and the primary site of productive BKPyV virus replication is the urothelium covering the human urinary tract [ 11 ].…”

Merkel Cell Polyomavirus (MCPyV) and Cancers: Emergency Bell or False Alarm?

“…Immunohistochemistry aims to differentiate MCCs from other, morphologically similar, neuroendocrine tumours through characteristic staining of a variety of MCC epithelial and neuroendocrine markers, such as cytokeratin-20 (CK20), neurofilaments, CAM 5.2, TTF-1 and AE1/3 [ 73 , 74 ]. With the purpose of distinguishing the VP-MCCs from VN-MCCs, a series of identification techniques are performed, including serological anti-oncoprotein antibody detection and molecular techniques of viral DNA amplification and detection (PCR, qPCR) [ 75 ]. For the molecular assays, the most common primers used target the LT and sT gene and the VP1 and NCCR regions of the genome [ 75 ].…”

“…With the purpose of distinguishing the VP-MCCs from VN-MCCs, a series of identification techniques are performed, including serological anti-oncoprotein antibody detection and molecular techniques of viral DNA amplification and detection (PCR, qPCR) [ 75 ]. For the molecular assays, the most common primers used target the LT and sT gene and the VP1 and NCCR regions of the genome [ 75 ]. Lastly, for confirmation purposes, a combination of molecular and immunohistochemical analyses can be performed (since viral proteins can be detected in tumour tissues) [ 75 ].…”

“…For the molecular assays, the most common primers used target the LT and sT gene and the VP1 and NCCR regions of the genome [ 75 ]. Lastly, for confirmation purposes, a combination of molecular and immunohistochemical analyses can be performed (since viral proteins can be detected in tumour tissues) [ 75 ]. On average, the viral genome copy number of MCPyV has been estimated to be 60 times lower in healthy tissues across the body compared to MCC samples [ 76 ].…”